A novel frameshift mutation in exon 6 (the site of Asn 291) of the lipoprotein lipase gene in type I hyperlipidemia.

A new heterozygous lipoprotein lipase gene defect has been identified in a type I hyperlipidemic patient at the position of notable amino acid Asn 291. The patient is a 33-year-old male. His body mass index (BMI) was 18.5 kg/m2. The total cholesterol (TC), triglycerides (TG) and high density lipoprotein-cholesterol (HDL-C) concentration from his fasting plasma were 4.8, 11.9 and 0.4 mmol/l, respectively. The lipoprotein lipase (LPL) activity and mass in the postheparin plasma (PHP) from the patient were 0.58 mmol/ml/h (normal range: 7.7+/-2.6) and 244 ng/ml (normal range: 192+/-30), respectively. The hepatic lipase activity of the PHP from the patient was 10.6 mmol/ml/h (normal range: 9.9+/-3.6). DNA analysis of the LPL gene revealed that this patient had a heterozygous one nucleotide deletion of A coding Asn 291, resulting in a premature termination of the LPL protein at amino acid residue 303. The other abnormality in the LPL gene of the proband was an amino acid residue 194 defect (Ile194-->Thr), which is known to cause a defective enzyme. A medium-chain triglyceride (MCT) loading test was conducted to find how this triglyceride affects plasma lipoprotein metabolism in this patient in a short term (Fig. 3). The plasma total cholesterol (TC) or high density lipoprotein (HDL)-C levels did not change significantly after oral administration of a fatty meal containing long chain triglycerides (LCT) or MCT. The plasma TG level, on the other hand, increased from 11.9 to 19.2 mmol/l (+61%) at 6 h after loading a fatty meal containing LCT, whereas the plasma TG levels tended to even decrease at 6 h after oral administration of an MCT, tricaprin (from 11.6 to 10.5 mmol/l (-9.4%)). These results suggest that MCT, as opposed to LCT, is useful for treatment of type I hyperlipidemia with a novel mutation at the notable amino acid Asn 291 of the LPL gene.     

Changes in cervical neutrophil elastase levels during the menstrual cycle

Purpose  

Cervical mucus plays an important role in host defense mechanisms and is involved in the ascendance of sperm. To determine the change of neutrophil mediators contained in cervical mucus, we measured total neutrophil elastase (NE) levels throughout the menstrual cycle.     

Studies of dialysates from Dermatophagoides farinae: partial purification and haptenic properties of dialysates from Dermatophagoides farinae.

Dialysates from Dermatophagoides farinae were partially purified. Fractionation on HPLC and anion exchange chromatography revealed that the dialysates consisted of 5 major fractions of glycoprotein whose apparent molecular sizes were 5.1, 4.1, 3.2, and less than 1.35 kD on HPLC. The apparent molecular size of two fractions was 5.3 and 2.9 kD on SDS-PAGE. They were basic glycoproteins which had a pI ranging from 7.46 to 8.71 on PAG-IEF. These fractions were allergenic in the RAST and ELISA inhibition tests but not in the skin prick test (SPT). Our results suggest that the dialysates from D. farinae have haptenic properties. The dialysates from D. farinae (low molecular weight) and its 5 fractions bound noncovalently to human serum albumin (HSA) at the free tyrosine residues of HSA. They proved to bind noncovalently to serum proteins and collagens. Once they bound to proteins, the conjugates became allergenic not only in the RAST and ELISA inhibition test but also in the SPT. Our results provide evidence that the dialysates from D. farinae have haptenic properties.     

Severe liver dysfunction possibly caused by the combination of interferon beta‐1b therapy and melilot (sweet clover) supplement

What is known and objective: We report a case of severe liver dysfunction exacerbated after interferon beta (IFNB)‐1b injection in a patient with multiple sclerosis (MS) who had been taking a melilot (sweet clover) supplement. Although IFNB‐1b therapy for MS can cause mild liver dysfunction, severe hepatotoxicity attributable to supplement use has been reported. Case summary: A 23‐year‐old Japanese woman taking a melilot supplement containing coumarin at 10 mg/day for 3 years was admitted to our hospital to receive IFNB‐1b therapy for MS. Fourteen days after subcutaneous injection of IFNB‐1b every other day, her aspartate transaminase (AST) and alanine aminotransferase (ALT) levels were elevated at 235 and 681 IU/L, respectively. After the discontinuation of IFNB‐1b therapy and supplement intake, AST and ALT returned to normal levels. Later, she started receiving an intramuscular injection of IFNB‐1a weekly without supplement intake. She was able to continue IFNB‐1a therapy this time, showing a slight elevation of AST level at 61 IU/L. What is new and conclusion: The combination of IFNB‐1b therapy and melilot supplement intake may cause severe liver dysfunction in patients with MS. Given the doubtful value of the supplement, we suggest that it should be avoided by patients receiving interferon therapy.     

Two cases of canine histoplasmosis in Japan]

Histoplasmosis is distributed in tropical, subtropical and temperate zones of the world. The disease is one of the imported mycoses in Japan. To date, although more than 30 human and one canine case of histoplasmosis have been reported in Japan, some including that of the canine might have been infected domestically, since the patients have no history of going abroad. The pathogen of histoplasmosis is thus believed to be present in our country. We examined skin biopsies from two dogs in Tokyo and Kumamoto, and found fungal elements 1-2 or 2-4 microEm in diameter in the macrophages. The homology of DNA sequences for the ITS rRNA gene were correspondent to Ajellomyces capsulatus at a rate of more than 97.4%. Therefore, the two dogs were diagnosed as having been infected with Histoplasma capsulatum which is the anamorph of A. capsulatus. Since the dogs had no history of having been outside Japan and had not been brought from an endemic area, they might have been infected domestically. Further epidemiological surveys on canine histoplasmosis may be able to estimate autochthonous human cases in Japan.     

Distinctive features of degenerating Purkinje cells in spinocerebellar ataxia type 31

Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant form of pure cerebellar ataxia that is caused by a disease‐specific insertion containing penta‐nucleotide repeats (TGGAA)_n. Neuropathologically, cerebellar Purkinje cells are preferentially affected and reduced in number in SCA31, and they are often surrounded by halo‐like amorphous materials. In the present study, we performed neuropathological analyses on two SCA31 brains, and discussed the serial morphological changes of Purkinje cells in SCA31.We found that bent, elongated, often folded nuclei were observed frequently in degenerating Purkinje cells with the halo‐like structure. Conversely, Purkinje cells without this structure developed marked atrophy with severely slender and condensed nuclei. On the basis of these pathological findings, we propose two different processes for Purkinje cell degeneration in SCA31, namely, shrinkage of Purkinje cells with or without the halo‐like amorphous materials. The former, but not the latter, was considered to be specific to SCA31. Correspondingly, fragmentation of the Golgi apparatus was observed more frequently in Purkinje cells with the halo‐like structure than in those without this structure. We consider that the profound nuclear deformity and fragmentation of the Golgi apparatus are closely linked with the formation of the halo‐like structure in SCA31.     

Sphingomyelin changes in rat cerebral cortex during focal ischemia

Abstract

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia. [Neurol Res 1996; 18: 337-341]